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This article is part of the supplement: Seventeenth Annual Computational Neuroscience Meeting: CNS*2008

Open Access Poster presentation

KA channels reduce dendritic depolarization from synchronized synaptic input: implication for neural processing and epilepsy

Jenny Tigerholm* and Erik Fransén

Author Affiliations

School of Computer Science and Communication, Royal Institute of Technology, Stockholm, Sweden

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BMC Neuroscience 2008, 9(Suppl 1):P45  doi:10.1186/1471-2202-9-S1-P45


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/9/S1/P45


Published:11 July 2008

© 2008 Tigerholm and Fransén; licensee BioMed Central Ltd.

Background

During cognitive tasks, synchrony of neural activity varies and is correlated with performance. There may however be an upper limit to the level of normal synchronicity and e.g., epileptogenic activity is characterized by excess spiking at high synchronicity. Furthermore with regard to neuronal excitability, synchronous input is the most effective input. In epilepsy an A-type potassium channel (KA) has been implicated. More specifically, a mutation in a KA gene was found in a temporal lobe epilepsy patient [1] and a highly selective blocker of KA induced seizures [2]. An objective of this work was to investigate if KAcould suppress synchronized synaptic input while minimally suppressing semi-synchronous input.

Methods

We used a cell model of a hippocampal CA1 pyramidal neuron based on Migliore et al [3]. It is composed of 566 compartments with Na, Kdr and KA -type currents of Hodgkin-Huxley type. Ten synaptic inputs were added on a medial compartment. The simulation was run for 1.5 s and repeated 15 times with different levels of synchronicity. To estimate the standard deviation, the procedure was repeated 20 times with different random seeds.

Results

See Figures 1 and 2

thumbnailFigure 1. Synchronized input is strongly suppressed by KA. The figure shows the number of spikes produced for different synchronicity levels. The dashed line represents baseline (control without KA) and the continuous line with KA. Note the pronounced suppression in the interval 100-90%.

thumbnailFigure 2. KA selectivity originates from its fast activation and slow inactivation. Activation of KA by synchronized versus semi-synchronized input. The continuous black lines represent synchronous input (100%), the gray lines semi-synchronous input (70%). The dashed lines represent values of KA steady-state activation and inactivation at the membrane potentials dictated in A. A: Membrane potential in the soma. B: Current through KA at input site. Note the difference in current around 4 ms. C: Inactivation of KA at input site. The interval 2–10 ms shows that the effect seen in B originates from the dynamical aspects of KA. D: Activation of KAat input site. Note activation around time of input 2–10 ms.

Discussion

Our model shows that KA differentially suppresses responses to varying levels of input synchrony. The study indicates that the selectivity of KA originates from its dynamic interaction between fast activation and slower inactivation in response to the waveform of a synchronized input, in the voltage region: -60 to -30 mV.

References

  1. Singh B, Ogiwara I, Kaneda M, Tokonami N, Mazaki E, Baba K, Matsuda K, Inoue Y, Yamakawa K: A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.

    Neurobiol Dis 2006, 24:245-53. PubMed Abstract | Publisher Full Text OpenURL

  2. Juhng K, Kokate T, Yamaguchi S, Kim B, Rogowski R, Blaustein M, Rogawski M: Induction of seizures by the potent K+ channel-blocking scorpion venom peptidetoxins tityustoxin-Kα and pandinustoxin-Kα.

    Epilepsy Res 1999, 34:177-186. PubMed Abstract | Publisher Full Text OpenURL

  3. Migliore M, Hoffman D, Magee J, Johnston D: Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons.

    J Comput Neurosci 1999, 7:5-15. PubMed Abstract | Publisher Full Text OpenURL